Wednesday, December 31, 2025 12/31/2025

Predictive multi-scale model of focal adhesion-based durotaxis

Award Number: R01GM148459
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/23/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

Predictive multi-scale model of focal adhesion-based durotaxis - Project Summary The over-arching goal of this proposal is to establish the predictive multi-scale mathematical model to decipher the mechanism of durotaxis. Durotaxis is the preference of cells migrating toward a stiffer extracellular matrix (ECM) and has important roles in many biological processes, ranging from embryo development to tumor metastasis. Focal adhesion (FA) is the functional unit of durotaxis; it an integrin-based multi-protein transmembrane linkage, through which cell exerts actin cytoskeleton-based traction force to tug the ECM and sense the stiffness. Despite the high relevance to biomedical applications, it is not well understood how FA mediates mechanosensing of ECM stiffness and drives durotaxis, largely because predictive mathematical models lag behind the descriptive experimental finding in the field. At single-FA level, while previous models explain molecular-clutch behaviors in FA mechanosensing, they cannot explain how and why FA- localized protein activities adapt to environments by distinctive spatial-temporal patterns (akin to footprints) that are demonstrated to be essential for durotaxis. The full underlying mechanisms of the FA-localized “footprint” and its exact roles in durotaxis are thus unknown. Further, durotaxis must coordinate movements of cell body and protrusion/retraction of cell edge. While the FA-mediated tractions drive the cell body, how the FA-localized mechanosensing events coordinate with the cell edge dynamics is unknown. Last, at a single-cell level, there exist many FAs at different developmental stages at any time. It is not understood how the cell integrates the mechanosensing activities of individual FAs to drive durotaxis. A predictive model that meaningfully engages with experiments is desirable and likely holds the key to decipher durotaxis. Toward this goal, we have been and will uniquely integrate mathematical modeling in iterative dialogues with experimental testing. The central hypothesis is: FA-localized spatial-temporal dynamics of the traction force generation and transmission defines FA-mediated mechanosensing and durotaxis. The basis of this proposal is our previous findings. We built the first mathematical model that captures the essence of entire FA maturation process. That is, FA evolves from a nascent complex, the centripetally growing FA that couples the retrograde flux of branching actin network, to the mature FA that transmits the stress fiber (SF)-mediated contractions onto ECM. This model uniquely links the FA-localized fine features of protein activities – emerging from FA maturation process – to FA mechanosensing events. The model predicted and was experimentally confirmed that a negative feedback between the elongation and contractility of the FA-engaging SF underlies the FA-localized traction oscillation and mechanosensing of ECM stiffness. Ushered by these findings, our specific aims are to determine: 1) how FA force-transmission and SF elongation cross-talk in FA mechanosensing; 2) how FA mechanosensing affects cell edge protrusion/retraction, and 3) how cell integrates mechanosensation of individual FAs to drive durotaxis. If successful, the proposed research would provide a quantitative platform interpret data and guide durotaxis experimental designs, which has the multi-scale resolutions ranging from FA-localized dynamics, cell edge protrusion/retraction, to cell movement at whole-cell level.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $343,806 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	4	12/16/2025	NON-COMPETING CONTINUATION	$343,806
														Subtotal = $343,806

Issue Date FY: 2025 ( Subtotal = $382,007 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	3	8/26/2025	NON-COMPETING CONTINUATION	$38,202
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	3	1/3/2025	NON-COMPETING CONTINUATION	$343,805
														Subtotal = $382,007

Issue Date FY: 2024 ( Subtotal = $382,007 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	2	7/23/2024	NON-COMPETING CONTINUATION	$38,202
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	2	12/29/2023	NON-COMPETING CONTINUATION	$343,805
														Subtotal = $382,007

Issue Date FY: 2023 ( Subtotal = $430,790 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	1	9/8/2023	SUPPLEMENT FOR EXPANSION	$32,845
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	1	1/23/2023	NEW	$397,945
														Subtotal = $430,790

Grand Total All Awards = $1,538,610

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Predictive multi-scale model of focal adhesion-based durotaxis

Award Number: R01GM148459

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/23/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer